Manufacturing and storing injectable medicines is difficult and costly, because they can be infectious or poisonous in their natural state. Exposure to heat and light needs to be managed in order to ensure that they remain sterile.[31] Experts generally agree upon many of the physical factors that contribute to these shortages:

The U.S. Government Accountability Office has noted that half of shortages due to manufacturing constraints were actually temporary shut-downs for improvements.[33] This helps explain why shortages of individual drugs are short-term. Shut-downs or slow-downs for unscheduled reasons include the discovery of bacteria or mold; the presence of inert foreign items like glass, metal or fibers in the vials; or the crystallization of the drug’s active ingredient.[34]

However, it is not clear how these physical problems could have become significantly worse since 2005, leaving us to examine regulatory changes that might have exacerbated the shortages.